Journal article
Effects of Combined Inorganic Nitrate and Nitrite Supplementation on Cardiorespiratory Fitness and Skeletal Muscle Oxidative Capacity in Type 2 Diabetes: A Pilot Randomized Controlled Trial
Nutrients, Vol.14(21), p.4479
10/25/2022
DOI: 10.3390/nu14214479
PMCID: PMC9654804
PMID: 36364742
Abstract
Nitric oxide (NO) stimulates mitochondrial biogenesis in skeletal muscle. However, NO metabolism is disrupted in individuals with type 2 diabetes mellitus (T2DM) potentially contributing to their decreased cardiorespiratory fitness (i.e., VO
2
max) and skeletal muscle oxidative capacity. We used a randomized, double-blind, placebo-controlled, 8-week trial with beetroot juice containing nitrate (NO
3
−
) and nitrite (NO
2
−
) (250 mg and 20 mg/day) to test potential benefits on VO
2
max and skeletal muscle oxidative capacity in T2DM. T2DM (N = 36, Age = 59 ± 9 years; BMI = 31.9 ± 5.0 kg/m
2
) and age- and BMI-matched non-diabetic controls (N = 15, Age = 60 ± 9 years; BMI = 29.5 ± 4.6 kg/m
2
) were studied. Mitochondrial respiratory capacity was assessed in muscle biopsies from a subgroup of T2DM and controls (N = 19 and N = 10, respectively). At baseline, T2DM had higher plasma NO
3
−
(100%;
p
< 0.001) and lower plasma NO
2
−
levels (−46.8%;
p
< 0.0001) than controls. VO
2
max was lower in T2DM (−26.4%;
p
< 0.001), as was maximal carbohydrate- and fatty acid-supported oxygen consumption in permeabilized muscle fibers (−26.1% and −25.5%, respectively;
p
< 0.05). NO
3
−
/NO
2
−
supplementation increased VO
2
max (5.3%;
p
< 0.01). Further, circulating NO
2
−
, but not NO
3
−
, positively correlated with VO
2
max after supplementation (R
2
= 0.40;
p
< 0.05). Within the NO
3
−
/NO
2
−
group, 42% of subjects presented improvements in both carbohydrate- and fatty acid-supported oxygen consumption in skeletal muscle (vs. 0% in placebo;
p
< 0.05). VO
2
max improvements in these individuals tended to be larger than in the rest of the NO
3
−
/NO
2
−
group (1.21 ± 0.51 mL/(kg*min) vs. 0.31 ± 0.10 mL/(kg*min);
p
= 0.09). NO
3
−
/NO
2
−
supplementation increases VO
2
max in T2DM individuals and improvements in skeletal muscle oxidative capacity appear to occur in those with more pronounced increases in VO
2
max.
Details
- Title: Subtitle
- Effects of Combined Inorganic Nitrate and Nitrite Supplementation on Cardiorespiratory Fitness and Skeletal Muscle Oxidative Capacity in Type 2 Diabetes: A Pilot Randomized Controlled Trial
- Creators
- Kristen D. Turner - University of IowaAna Kronemberger - University of IowaDam Bae - Department of Health and Human Physiology, College of Liberal Arts and Sciences, University of Iowa, Iowa City, IA 52242, USA Department of Physical Therapy and Rehabilitation Science, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA Department of Anesthesia, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA 52242, USA Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, IA 52242, USA François M. Abboud Cardiovascular Research Center, University of Iowa, Iowa City, IA 52242, USA Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, IA 52242, USA Obesity Research and Education Initiative, University of Iowa, Iowa City, IA 52242, USAJoshua M. Bock - University of IowaWilliam E. Hughes - University of IowaKenichi Ueda - University of IowaAndrew J. Feider - University of IowaSatoshi Hanada - University of IowaLuis G. O. de Sousa - Department of Health and Human Physiology, College of Liberal Arts and Sciences, University of Iowa, Iowa City, IA 52242, USA Department of Physical Therapy and Rehabilitation Science, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA Department of Anesthesia, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA 52242, USA Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, IA 52242, USA François M. Abboud Cardiovascular Research Center, University of Iowa, Iowa City, IA 52242, USA Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, IA 52242, USA Obesity Research and Education Initiative, University of Iowa, Iowa City, IA 52242, USAMatthew P. Harris - University of IowaEthan J. Anderson - University of IowaSue C Bodine - University of IowaM. Bridget Zimmerman - University of IowaDarren P. Casey - University of IowaVitor A. Lira - Department of Health and Human Physiology, College of Liberal Arts and Sciences, University of Iowa, Iowa City, IA 52242, USA Department of Physical Therapy and Rehabilitation Science, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA Department of Anesthesia, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA 52242, USA Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, IA 52242, USA François M. Abboud Cardiovascular Research Center, University of Iowa, Iowa City, IA 52242, USA Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, IA 52242, USA Obesity Research and Education Initiative, University of Iowa, Iowa City, IA 52242, USA
- Resource Type
- Journal article
- Publication Details
- Nutrients, Vol.14(21), p.4479
- DOI
- 10.3390/nu14214479
- PMID
- 36364742
- PMCID
- PMC9654804
- NLM abbreviation
- Nutrients
- eISSN
- 2072-6643
- Publisher
- MDPI
- Grant note
- 1-16-1CTS-015 / American Diabetes Association R56AG063820; P30 CA086862 / National Institutes of Health
- Language
- English
- Date published
- 10/25/2022
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics; Biostatistics; Anesthesia; Physical Therapy and Rehabilitation Science; Fraternal Order of Eagles Diabetes Research Center; Dental Research; Endocrinology and Metabolism; Health, Sport, and Human Physiology ; Internal Medicine
- Record Identifier
- 9984314305602771
Metrics
72 Record Views